Brandi M Wynne1,2, Cameron G McCarthy3, Theodora Szasz3, Patrick A Molina1, Arlene B Chapman4, R Clinton Webb3, Janet D Klein1,2, Robert S Hoover1,2,5. 1. Renal Division, Department of Medicine. 2. Department of Physiology, Emory University, Atlanta. 3. Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia. 4. Department of Medicine, Nephrology, University of Chicago, Chicago, Illinois. 5. Research Service, Atlanta Veteran's Administration Medical Center, Decatur, Georgia, USA.
Abstract
AIM: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility. METHODS: Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. RESULTS: PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. CONCLUSION: Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.
AIM: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility. METHODS: Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. RESULTS: PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. CONCLUSION: Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.
Authors: Hui-Fang Bao; Tiffany L Thai; Qiang Yue; He-Ping Ma; Amity F Eaton; Hui Cai; Janet D Klein; Jeff M Sands; Douglas C Eaton Journal: Am J Physiol Renal Physiol Date: 2013-12-11
Authors: Julio D Duarte; Issam Zineh; Ben Burkley; Yan Gong; Taimour Y Langaee; Stephen T Turner; Arlene B Chapman; Eric Boerwinkle; John G Gums; Rhonda M Cooper-Dehoff; Amber L Beitelshees; Kent R Bailey; Roger B Fillingim; Bruce C Kone; Julie A Johnson Journal: J Transl Med Date: 2012-03-22 Impact factor: 5.531